Hsc70 regulates the IRES activity and serves as an antiviral target of enterovirus A71 infection

Dong, Qi; Men, Ruoting; Dan, Xuelian; Chen, Ying; Li, Huangcan; Chen, Gong; Zee, Benny; Wang, Maggie Haitian; He, Ming‐Liang

doi:10.1016/j.antiviral.2017.11.020

Cited by 27 publications

(32 citation statements)

References 41 publications

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“…Virus entry RNA virus: CAV-9, 186 EV-A71, 188 DENV, 110,189 JEV, 191 ZIKV 190,197 DNA virus: SV40, 234 AdV, 237 HSV, 241 polyomavirus 254 RT virus: HTLV-1, 258,259 HIV-1 260 Virus replication RNA virus: MuV, 201 CDV, 203,204 HCV, 206 RSV, 209 EBOV, 212,213 Influenza 217 Virus gene expression RNA virus: Coxsackievirus B3, 218 EV-A71, 219 Influenza A [222][223][224][225][226] DNA virus: Polyomavirus, JCV, HCMV, 245,[246][247][248][249] Assembly RNA virus: Reovirus, 227 Poliovirus, 228 Coxsackievirus B1, 228 Influenza 229 DNA virus: Polyomavirus 254 Virus release RNA virus: HCV 232,233 Cellular transformation DNA virus: SV40, [264][265][266][267]…”

Section: The Function Of Hsp90 Family In Virus Infectionmentioning

confidence: 99%

“…Hsc70 interacts with 2A protease of EV-A71 to enhance EIF4G cleavage that impairs host cell cap-dependent translation but enhances viral IRES-mediated translation. 219 Therefore, Hsc70 may serve as an antiviral target against EV-A71 and HCV infections. Some viruses do not have IRES sequence, and virus replication produces plenty of dsRNAs which trigger the activation of protein kinase-RNA-activated (PKR)-EIF2a signalling cascade that shuts down global translation in cells and releases stresses.…”

Section: The Function Of Hsp70 Family In Virus Infectionmentioning

confidence: 99%

“…582 EV-A71 takes advantage of HSPs (Hsp90, HSc70, ERp57, and Hsp27) to enhance 2A pro -mediated eIF4G cleavage that is favour viral protein translation and blocks host protein translation. 57,219,415 Viruses also initiate ER stress in host cells after infection. They have to manipulate UPR activation leading to cell survival, rather than inflammation induction, autophagy and apoptosis.…”

Section: Challenges Of Targeting Stress Proteins For Antiviral Therapymentioning

confidence: 99%

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Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

Wan

Song

et al. 2020

Sig Transduct Target Ther

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Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histonelike nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson's diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation.

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Section: The Function Of Hsp90 Family In Virus Infectionmentioning

confidence: 99%

Section: The Function Of Hsp70 Family In Virus Infectionmentioning

confidence: 99%

Section: Challenges Of Targeting Stress Proteins For Antiviral Therapymentioning

confidence: 99%

See 1 more Smart Citation

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

Wan

Song

et al. 2020

Sig Transduct Target Ther

Self Cite

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“…Evidence is growing that exposure of cells and tissues to low ambient temperature leads to transcription and translation of heat shock proteins 70 KDa (Hsp70) [9][10][11][12][13][14]. Moreover, Hsp70 has been shown to be one key factor for multiple virus infection including rabies virus [15], porcine circovirus type 2 [16], porcine reproductive and respiratory syndrome virus [17], influenza A virus [18], dengue virus [19], infectious bronchitis virus [20], Epstein-Barr virus [21], ectromelia virus [22], hepatitis B virus [23], enterovirus A71 [24] and zika virus [25,26]. Hsp70 plays important role in many steps of viral life cycle, including entry [27,28], uncoating [29], replication of the viral genome [30,31], gene expression [32] and virion morphogenesis [33,34].…”

Section: Introductionmentioning

confidence: 99%

Cold Exposure-Induced Up-Regulation of Hsp70 Positively Regulates PEDV mRNA Synthesis and Protein Expression In Vitro

Kong

Wei

et al. 2020

Pathogens

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Porcine epidemic diarrhea (PED) is a highly contagious, intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV). PEDV as an emerging and re-emerging epizootic virus of swine causes substantial economic losses to the pig industry in China and other countries. In China, the occurrence of PED shows significant seasonal variations, usually outbreak during the winter season. The epidemic characteristics of PED may be highly correlated with the changes of ambient temperature. However, molecular mechanism on the seasonal occurrence of PED still remains unclear. It has been widely observed that low ambient temperature up-regulates the expression of host heat shock protein 70 (Hsp70). Here, we showed that nucleotide and protein levels of Hsp70 were up-regulated in the intestinal of cold exposed pig and cold exposed Vero E6 cells. We found that overexpression of Hsp70 could increase PEDV mRNA synthesis and protein expression in Vero E6 and IPEC-J2 cells, while the siRNAs mediated knockdown of Hsp70 and VER155008 mediated inhibition of Hsp70 resulted in inhibition of viral mRNA synthesis and protein expression in Vero E6 cells. These data suggested that Hsp70 positively regulated PEDV mRNA synthesis and protein expression, which being helpful for understanding the seasonality of PED epidemics and development of novel antiviral therapies in the future.

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“…4). After EV-A71 infection, Hsc70 also enhances viral 2A pro activity to promote viral IRES activity [54]. DDX3 is a member of the DEAD-box RNA helicase family.…”

Section: Hsp27mentioning

confidence: 99%

Translation control of Enterovirus A71 gene expression

Lai

Chen

et al. 2020

J Biomed Sci

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Upon EV-A71 infection of a host cell, EV-A71 RNA is translated into a viral polyprotein. Although EV-A71 can use the cellular translation machinery to produce viral proteins, unlike cellular translation, which is capdependent, the viral RNA genome of EV-A71 does not contain a 5′ cap and the translation of EV-A71 protein is cap-independent, which is mediated by the internal ribosomal entry site (IRES) located in the 5′ UTR of EV-A71 mRNA. Like many other eukaryotic viruses, EV-A71 manipulates the host cell translation devices, using an elegant RNA-centric strategy in infected cells. During viral translation, viral RNA plays an important role in controlling the stage of protein synthesis. In addition, due to the cellular defense mechanism, viral replication is limited by down-regulating translation. EV-A71 also utilizes protein factors in the host to overcome antiviral responses or even use them to promote viral translation rather than host cell translation. In this review, we provide an introduction to the known strategies for EV-A71 to exploit cellular translation mechanisms.

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Hsc70 regulates the IRES activity and serves as an antiviral target of enterovirus A71 infection

Cited by 27 publications

References 41 publications

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

Cold Exposure-Induced Up-Regulation of Hsp70 Positively Regulates PEDV mRNA Synthesis and Protein Expression In Vitro

Translation control of Enterovirus A71 gene expression

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